On Cancer Risk and the Hierarchical Architecture of Tissues

Abstract

Tomasetti and Vogelstein (Science, 2 Jan. 2015, p. 78) demonstrated that cancer risk in different tissues is correlated with the total number of stem cell divisions, and concluded that the majority of cancer risk is attributable to “bad luck”. Here we show that their interpretation of the observed correlation is fundamentally flawed, and a thousand fold variation in risk remains after accounting for differences in the total number of stem cell divisions. We also explore possible explanations for the observed slower than linear increase of cancer risk with the total number of stem cell divisions and argue that this is the result of “Peto's paradox among somatic tissues”.During each division cells are subject to mutations, thus constantly renewing tissues inevitably accumulate mutations over time, which can potentially lead to the development of cancer. Here we show that the theoretical minimum of the number of cell divisions during tissue maintenance over a lifetime can be closely approached with a hierarchical tissue architecture. Thus, one of the main reasons of the existence of such hierarchical architecture in multicellular organisms is to minimize somatic evolution and prevent cancer. Such a hierarchical architecture is also vital in the germline (e.g. in spermatogenesis) to minimize the number of mutations passed on to the next generation.